The broad objective of this research program is a better understanding of the physio logical processes involved in the reactions of the cardiovascular and pulmonary systems to stress. Stresses which commonly play on these systems include physical exercise, change in environment, and disease states of the heart, blood vessels, and lungs. The principal function of these combined systems, (cardiovascular- pulmonary) is to furnish the required oxygen to the various tissues of the body. Thus our goal is to study quantitatively the mechanisms which regulate and limit the oxygen transport system in the body. Currently various experiments are being conducted on multiple levels including the integrated response to stress in normal subjects and in patients with cardiovascular disease. Also more detailed and controlled studies are being performed in intact animals, isolated organs, and tissue preparations. Such a broad attack directed to all links in the oxygen transport system should establish a more sound physiological basis for classification and quantitation of therapeutic methods. Close contact and cooperation between the members of the group primarily concerned with clinical research problems and those who are working in the basic areas of physiology and biochemistry provide the background considered essential for successful continuation of this program.